CD8+ T cells protect against CVB3 infection in females.

Coxsackievirus B3 (CVB3) is the primary cause of viral myocarditis, and approximately 5% of symptomatic CVB3 infections are fatal. CVB3 infection also exhibits a strong sex bias, with males showing increased susceptibility to disease, which is incompletely understood. Despite these burdens, there are no vaccines or treatments available for Coxsackievirus infections. Using an oral inoculation mouse model to recapitulate natural infection, we demonstrated a sex bias where male mice succumb to CVB3-induced disease at an increased rate than female mice, consistent with human infections. Here we make the novel observation that CVB3 induces the expansion of antigen-experienced CD8+ T cells in female mice but not in male mice. The CD8+ T cells in female mice have an activated phenotype following infection, and we demonstrate that these T cells protect female mice from CVB3-induced mortality. Overall, our findings emphasize the importance of evaluating sex differences in the immune response to viral pathogens and may have implications for future T cell vaccine strategies.